The program in "Developmental and Pediatric Clinical Pharmacology" will attempt to develop a body of knowledge pertaining to the effects and disposition of pharmacologically active molecules in the developing mammal. Pre-clinical investigations will be integrated wherever possible with parallel studies in the human. The primary objective of this approach is to develop animal models with predictive potential for comparable age groups in the human. The data developed in the experimental model will be used as a base for the establishment of rational guidelines for drug utilization in the pregnant woman, young infant, and developing child. An integral component of the overall program is the development of new methodologic approaches specifically designed for the analysis of drug disposition in immature organisms. These methods are based primarily upon microanalytical procedures utilizing column chromatography (high pressure liquid and gas chromatography/mass spectrometry, high pressure liquid chromatography/mass spectrometry, electrochemical detection and immunoassay). Specific investigational areas to be considered during the tenure of this program are the following: 1) Placental transfer and pharmacodynamics of drugs in the maternal-placental-fetal unit, e.g. chemotherapeutic agents (sulfonamides, antibiotics); cardiovascular agents (propranolol, digoxin). 2) Pharmacokinetics and disposition of drugs in the immature organism, e.g. cardiovascular drugs (propranolol, digoxin, theophylline, methyldopa, hydrochlorothiazide). 3) Hypertension and biological maturation; effects of antihypertensive therapy. 4) Clinical correlative studies pertaining to each of the basic areas under investigation have been carried out.